The Mycobacterium genus includes numerous bacterial species that cause disease in man, other mammals, and birds. For example, M. tuberculosis is the causative agent of the most common infectious disease in the world today, tuberculosis. The World Health Organization (WHO) reported that 1.7 billion people (or approximately one-third of the world's population) are or have been infected at one point in their lives by M. tuberculosis. Kochi, A. Tubercle 72:1-6 (1991). It is estimated that 10 to 15 million people in the U.S. have latent infections. Morbidity and Mortality Weekly Report 39(RR-8):9-12 (1990). It is calculated that 8 million new clinical tuberculosis cases occur worldwide per year and approximately 3 million people die annually. Morbidity and Mortality Weekly Report 42 (49):961-964 (1993).
Mycobacteria of the MAC complex (primarily M. avium and M. intracellulare) are opportunistic pathogens in AIDS patients. Approximately 43% of AIDS patients at advanced stages of the disease suffer MAC infections. Nightingale et al., J. Infect. Dis. 165:1082-1085 (1992). In addition to AIDS related infections, M. paratuberculosis, a subspecies of M. avium is thought to be associated with Crohn's disease, an inflammatory disease of the bowel. Chiodini, R. J. Clin. Micro. Rev. 2:90-117 (1989).
Additional mycobacteria which are considered human pathogens, include M. leprae, M. kansasii, M. marinum, M. fortuitum complex, M. bovis, M. scrofulaceu, and M. ulcerans. Baron, S., editor, MEDICAL MICROBIOLOGY, Second Edition, pages 562-564 Addison-Wesley Pub. Co., Menlo Park, Calif. (1996); Wayne, L. G. et al., Clin. Micro. Rev. 5:1-25 (1992). There are an estimated 5.5 million cases of M. leprae infections worldwide. Nordeen, S. K. et al., Int. J. Lepr. 63:282-287 (1993).
M. paratuberculosis also causes bowel inflammations in ruminants, more commonly known as Johne's disease. Thoen, C. O. et al., Rev. Infect. Dis. 3:960-972 (1981). Cattle that test positive for M. paratuberculosi are culled and destroyed. The incidence among herds nationwide typically ranges between 3% and 18%. Merkal, R. S. et al., J. Am. Vet. Med. Assoc. 190:676-680 (1987). The financial impact of this disease on the dairy industry exceeds $1.5 billion annually. Whitlock, R. PROCEED. OF THE THIRD INTERNAT. COLLOQ. PARATUBERCUL., pp.514-522 (1991). M. bovis is another mycobacteria of importance in veterinary medicine. M. fortuitum is a soil bacterium that has been isolated from lesions in animals and humans. M. avium causes a disease in chicken, a serious concern to the poultry industry. M. marinum infects cold-blooded animals and fish; it has also been isolated from superficial granulomas on the extremities of humans.
Extracts from several hundred plant species have been tested to date for anti-cancerous, anti-microbial, anti-bacterial and, sometimes, anti-mycobacterial activity. The total extract or, sometimes the oil from plant tissue ranging from leaf, stem, and root, were shown to have various levels of activity. In most cases, the chemical composition of the material has not been described. For a review, see Newton et al., Phytother. Res., 14:303-322 (2000). See also Soliman et al., Flavour and Fragrance Journal, 9(1): 29-33 (1994); Hebda, Dissertation Abstracts International, 53(4-C): 737 (1991); Robbs, Dissertation Abstracts International, 58(6-B): 3009 (1997); Kurtulik, Dissertation Abstracts International, 43(4-B): 1050 (1982); Oguntimein, Dissertation Abstracts International, 42(02-B): 577 (1981); Frame et al., P. R. Health Sci. J., 17: 243-252 (1998); Lall et al., J Ethnopharmacol, 66: 347-354 (1999); and Rastogi et al., FEMS Immuno. Med. Microbiol. 20: 267-273 (1998). Thus, a need for identification of pure and effective anti-mycobacterial chemical compounds remains. Generally, the results were disappointing in regard to identification of lead plant extracts with anti-mycobacterial activity. See Newton (2000) supra. However, see Rejab et al., Phytotherapy Research, 14: 303-322 (2000), George et al., Phytotherapy Research, 14: 303-322 (2000), and Lall et al, supra.
The lipoidal nature of the mycobacterial cell wall appears to contribute to survival of mycobacteria by rendering them resistant to drying and acid or alkaline conditions. For example, mycobacteria survive acid or alkaline conditions and heat sterilization of limited duration. Mycobacterium has proved to be a tough, difficult to control bacteria. New infective mycobacteria can be retrieved after several months from old cultures or contaminated surfaces. New agents that can control mycobacterial contamination are needed.
A new fear of tuberculosis has resulted from reports about outbreaks with multidrug resistant strains of M. tuberculosis (MTB) in the United States. These strains are resistant to at least the most important antituberculotic drugs, isoniacid and rifampicin. The frequency of multidrug-resistant tuberculosis in the USA is reported to be 3-7% and about 19% in New York. Thus there is an urgent need for new and effective antimycobacterial agents to replace or add to those currently in use.